Purpose of Review Inappropriate and unnecessary antibiotic prescriptions are common in the outpatient setting and as patients transition from inpatient to outpatient care. This review is designed to discuss effective strategies aimed to improve appropriate antibiotic use during transitions of care and in the outpatient setting for high-priority syndrome areas including acute respiratory infections (ARI), urinary tract infections (UTI), skin and soft tissue infections (SSTI), and bone and joint infections (BJI). Recent Findings Unlike inpatient stewardship programs, outpatient stewardship practices are currently not standardized across many healthcare systems. Since starting an outpatient ASP can be overwhelming, many programs opt to start by focusing on a smaller subset of high-priority locations or syndromes where antibiotics may be inappropriately prescribed. Numerous studies have identified effective antimicrobial stewardship strategies that can be incorporated on transitions of care and in the outpatient setting; however, a multimodal approach combining several stewardship strategies is often cited as the most effective approach. Available syndrome-specific interventions include opportunities at time of diagnosis, order entry, and post-prescription which may be tailored to meet individual program needs. Summary Outpatient ASP interventions targeted at diagnostic stewardship, adjustments to duration of therapy, optimization of agent selection, and avoidance of intravenous therapy remain high-priority target areas to prevent inappropriate antibiotic use.

Numerous patients have cultures pending at discharge which, if not addressed, may delay diagnosis and initiation of appropriate antimicrobials. The purpose of the study is to evaluate the appropriateness of discharge antimicrobial therapy and result documentation in patients with positive cultures finalized post-discharge. This was a cross-sectional cohort study of patients admitted from July 1 to December 31, 2019 with positive sterile-site microbiologic cultures finalized post-discharge. Pertinent inclusion and exclusion factors were admission ≥ 48 h and non-sterile sites, respectively. The primary objective was to determine the frequency of discharged patients warranting antimicrobial changes based on finalized cultures. Secondary objectives included prevalence and timeliness of result documentation and rates of 30-day readmission, among intervention warranted versus not warranted. Chi-squared or Fisher’s exact tests were used as appropriate. Binary multivariable logistic regression was completed for 30-day readmission stratified by infectious disease (ID) involvement due to the potential for effect modification. A total of 208 of 768 patients screened were included. Most patients were discharged from a surgical service (45.7

Objectives We evaluated the clinical characteristics and outcomes of patients with COVID-19 who received three-drug combination regimens for treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections during a single-centre outbreak. Our objective was to describe the clinical outcomes and molecular characteristics and in vitro synergy of antibiotics against CRAB isolates. Materials and methods Patients with severe COVID-19 admitted between April and July 2020 with CRAB infections were retrospectively evaluated. Clinical success was defined as resolution of signs/symptoms of infection without need for additional antibiotics. Representative isolates underwent whole-genome sequencing (WGS) and in vitro synergy of two- or three-drug combinations was assessed by checkerboard and time-kill assays, respectively. Results Eighteen patients with CRAB pneumonia or bacteraemia were included. Treatment regimens included high-dose ampicillin-sulbactam, meropenem, plus polymyxin B (SUL/MEM/PMB; 72%), SUL/PMB plus minocycline (MIN; 17%) or other combinations (12%). Clinical resolution was achieved in 50% of patients and 30-day mortality was 22% (4/18). Seven patients had recurrent infections, during which further antimicrobial resistance to SUL or PMB was not evident. PMB/SUL was the most active two-drug combination by checkerboard. Paired isolates collected before and after treatment with SUL/MEM/PMB did not demonstrate new gene mutations or differences in the activity of two- or three-drug combinations. Conclusions Use of three-drug regimens for severe CRAB infections among COVID-19 resulted in high rates of clinical response and low mortality relative to previous studies. The emergence of further antibiotic resistance was not detected phenotypically or through WGS analysis. Additional studies are needed to elucidate preferred antibiotic combinations linked to the molecular characteristics of infecting strains.

Abstract Background Clinical guidelines for antimicrobial prophylaxis recommend use of cefazolin for most surgical procedures. Patients who are labeled penicillin (PCN) allergic are often prescribed second line agents, though cross-reactivity is less than 1%. PCN allergic patients have significantly higher rates of readmissions and healthcare-associated infections. Allergy documentation in the medical record is often incomplete or inaccurate, and many allergies can be de-labeled through history alone. Our study aimed to investigate accuracy of allergy risk assessment in PCN allergic patients and the impact on surgical antibiotic prophylaxis for quality improvement. Methods This was a retrospective observational cohort study among adult patients with a reported PCN allergy who underwent a surgical procedure from 3/2019-2/2020 at a single academic institution. The primary outcome was incidence of appropriate documentation of allergy risk severity. Secondary outcomes included receipt of beta-lactam for surgical prophylaxis and incidence of documentation to reflect tolerance. Allergy risk classification was considered appropriate if it aligned with institutional guidelines (Table 1). Results Of 2647 patients who underwent surgical procedures, 330 (12%) reported PCN allergy. Allergy risk severity was appropriately documented in 136 (41%) patients. 150 (45%) were mislabeled as “high” or “unknown” risk compared to reported reaction. 191 (58%) patients with reported PCN allergies received beta-lactam antibiotics peri-operatively. Allergy history had been updated to reflect tolerance in only 6% of patients who received cefazolin for surgical prophylaxis and in 21% who had received beta-lactams previously (Table 2). Table 2:Primary and Secondary Outcomes Conclusion Inaccurate documentation of allergy risk results in decreased first-line antimicrobial use in patients with reported PCN allergies. Documented PCN allergy risk severity was often incorrect and over 100 additional patients could have been labeled “low risk” based on reported reaction. 72% of patients could have received first-line beta-lactam prophylaxis per institutional guidelines. Interventions targeting allergy history documentation alone could positively impact antibiotic selection. Disclosures All Authors: No reported disclosures.

Abstract Background Half of patients have cultures pending at discharge. Failure to address these results may delay diagnosis and time to appropriate antimicrobials. The purpose of the study is to evaluate appropriateness of antimicrobial therapy and result documentation in patients with positive cultures finalized post-discharge. Methods Retrospective cohort study of patients from 7/2019-12/2019 with positive sterile-site microbiologic cultures finalized post-discharge. Pertinent inclusion and exclusion factors were admission ≥48 hours and non-sterile sites, respectively. The primary objective was to determine the frequency of discharged patients warranting antimicrobial intervention based on finalized culture results. Secondary objectives included incidence and timeliness of result documentation and rates of 30-day hospital readmission, among intervention warranted vs not warranted. Chi-squared or Fisher’s exact tests were used as appropriate. Binary multivariable logistic regression was completed for 30-day hospital re-admission stratified by infectious disease (ID) team involvement. Results 208 of 768 patients screened were included. Most patients were discharged from a surgical service (45.7%); deep tissue and blood were the most common culture sites (29.3%). Antimicrobial intervention was warranted in 36.5% of patients (n=76). Rates of result documentation were overall low (35.5%). Time to documentation of results was significantly shorter in patients warranting intervention compared to those who did not, but hospital readmission was higher (Table 1). Finally, result documentation in patients not being followed by ID was associated with decreased odds of 30-day readmission (OR 0.19, 95% CI, 0.07-0.53) (Table 2). Conclusion A significant number of patients with cultures finalized post-discharge warranted antimicrobial intervention. Acknowledgment of final culture data can decrease the risk of 30-day hospital readmission, especially in patients not followed by ID. Quality improvement efforts should focus on methods to improve documentation and follow-up of pending cultures to improve patient outcomes. Disclosures Kimberly C. Claeys, PharmD, BioFire Diagnostics: Honoraria|La Jolla Pharmaceuticals: Advisor/Consultant.

External urinary collection devices (ECDs) are increasingly used in female patients, however, their impact on bacteriuria and antimicrobial use is unclear. Comparing the periods before and after the implementation of an ECD use policy, we found an overall decrease in bacteriuria but no significant decrease in trend of monthly rates. Antimicrobial use for genitourinary indications did not change.

We report a case of septic shock attributable to monomicrobial bloodstream infection secondary to Wohlfahrtiimonas chitiniclastica infection. This case suggests that W. chitiniclastica likely possesses the virulence to cause severe disease. Culture-independent techniques were essential in the identification of this organism, which enabled selection of appropriate therapy.

Revised breakpoints for cefazolin (CFZ) against Enterobacterales may be difficult to implement with current automated susceptibility testing platforms and could falsely report organisms as susceptible, leading to inappropriate treatment for bloodstream infections (BSI). This was a retrospective cohort of adult patients with Enterobacterales BSI reported CFZ susceptible per Vitek®2. The primary outcome was the percentage susceptible by minimum inhibitory concentration (MIC) Gradient Test Strips and disk diffusion. Secondary outcomes included clinical outcomes between CFZ and non–CFZ-treated patients. Among 195 isolates reported CFZ-susceptible per Vitek®2, 84 (43.1%) were CFZ susceptible by MIC Gradient Test Strips vs 119 (61%) by disk diffusion. No difference was noted in 30-day all-cause mortality, secondary complications, or 30-day readmissions. Treatment failure was less likely to occur with source control (adjusted OR 0.06) and infectious disease consult (adjusted OR 0.37). There was a large degree of discrepancy between automated testing and manual methods; the clinical impact of this discrepancy warrants further investigation.

Abstract Background Molecular rapid diagnostic tests (RDTs) for bloodstream infections (BSI) utilize a variety of technologies and differ substantially in organisms and resistance mechanisms detected. RDT platforms decrease time to optimal antibiotics; however, data on RDTs in special populations, such as immunocompromised are extremely limited. This study aimed to compare theoretical changes in antibiotics based on differences in panel identification of organisms and resistance targets among three commercially available RDT panels. Methods Retrospective cohort of immunocompromised patients treated for gram-negative BSI at University of Maryland Medical Center from January 2018 to September 2020. Immunocompromised was defined as active hematologic or solid tumor malignancy at time of BSI diagnosis, history of hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT), or absolute neutrophil count (ANC) < 1000 cells/mm3 at any time 30 days prior to BSI diagnosis. Verigene BC-GN was performed as standard of care. GenMark ePlex BCID and BioFire FilmArray BCID 2 results were assigned based on respective identifiable organism panels. An infectious diseases clinician blinded to final antimicrobial susceptibility testing (AST) results used RDT results to assign antibiotic treatments for each platform. Decisions were referenced against a priori DOOR-MAT matrices. A partial credit scoring system (0 to 100) was applied to each decision based on final AST results. The mean and standard deviation (SD) were compared across panels using One-Way Repeated Measures ANOVA with modified Bonferroni for multiple comparisons. Results A total of 146 patients met inclusion. Baseline characteristics are summarized in Table 1. The mean (SD) DOOR-MAT scores for the three RDT panels were: 86.1 (24.4) Verigene BC-GN vs. 88.5 (22.2) GenMark BCID vs. 87.2 (24.4) BioFire BCID 2. There was no statistically significant difference between the panels for DOOR-MAT score (P=0.6). Table 1. Baseline Patient Characteristics and Organism Identification Conclusion Within an immunocompromised patient population, differences in organism identification between three commercially available RDT panels did not impact theoretical antibiotic prescribing. Disclosures J. Kristie Johnson, PhD, D(ABMM), GenMark (Speaker’s Bureau) Kimberly C. Claeys, PharmD, GenMark (Speaker’s Bureau)

A 25-year-old male presented with profound hypoxemia despite use of a non-rebreather mask during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Chest X-ray showed a large right pneumothorax and extensive interstitial disease (Figure 1a). Hypoxemia continued despite chest tube placement, necessitating emergent intubation. Computed tomography (CT) of the chest (Figure 1b–d) was obtained and nasopharyngeal SARS-CoV-2 PCR was positive. HIV serology was positive and his absolute CD4+ count was 32 cells/mm3. Given his severe acquired immunodeficiency, radiographic findings were concerning for a life-threatening co-infection with Pneumocystis jirovecii, and treatment with trimethoprim–sulfamethoxazole, prednisone, and remdesivir was started. Four days later, Pneumocystis pneumonia (PCP) was confirmed by bronchoscopic Pneumocystis antigen. The patient improved clinically and was successfully extubated 21 days later. Multifocal ground-glass opacities are the principal finding in both PCP and SARS-CoV-2 infection, making radiographic differentiation potentially difficult, especially in the immunocompromised host (Shi et al., 2020Shi H. Han X. Jiang H. Cao Y. Alwalid O. Gu J. et al.Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study.Lancet Infect Dis. 2020; 20: 425-434Abstract Full Text Full Text PDF PubMed Scopus (2476) Google Scholar, Zu et al., 2020Zu Z. Jiang M. Xu P. Chen W. Ni Q. Lu G. et al.Coronavirus disease 2019 (COVID-19): a perspective from China.Radiology. 2020; 200490https://doi.org/10.1148/radiol.2020200490Crossref Scopus (1187) Google Scholar, Thomas and Limper, 2004Thomas C.F. Limper A.H. Pneumocystis pneumonia.N Engl J Med. 2004; 350: 2487-2498Crossref PubMed Scopus (863) Google Scholar, Kanne et al., 2012Kanne J. Yandow D. Meyer C. et al.Pneumocystis jiroveci pneumonia: high-resolution CT findings in patients with and without HIV infection.AJR. 2012; 198: W555-W561Crossref PubMed Scopus (160) Google Scholar). Cystic lesions can occur in one third of patients with advanced PCP (Kanne et al., 2012Kanne J. Yandow D. Meyer C. et al.Pneumocystis jiroveci pneumonia: high-resolution CT findings in patients with and without HIV infection.AJR. 2012; 198: W555-W561Crossref PubMed Scopus (160) Google Scholar). In the absence of these cystic radiographic findings, the diagnosis of Pneumocystis jirovecii co-infection would have been arduous. Therefore awareness of co-infections is critically important in the current SARS-CoV-2 pandemic to properly diagnose and subsequently treat these co-infections, thereby reducing morbidity and mortality. None.

Bacteriuria associated with indwelling urinary catheters is commonly linked to inappropriate antibiotic use in hospitals. The use of external catheter devices (ECD) has increased in recent years to reduce bacteriuria risk in women, based on data in male patients. Currently no studies have shown a similar benefit in the female population. This was a quasi-experimental study among adult female ICU patients with urinary catheters (indwelling or external) between 12/2015 – 5/2017 (pre-ECD) and 12/2017 – 6/2019 (post-ECD). The primary outcome was the incidence of positive urine cultures pre- vs post-intervention. An a priori subgroup patient-level analysis evaluated positive urine cultures and antibiotic use pre- vs post-intervention in medical and surgical ICU patients who had a urinalysis ordered in the presence of an indwelling or external urinary catheter. Antibiotic use was considered appropriate when prescribed in the presence of a positive urine culture, clinical signs and symptoms of UTI, and a UTI order indication. There were 4,640 patient ICU encounters during the study period; 2,201 pre- vs 2,439 post-intervention. Mean age was 59.2 (SD 15.4) years, median Elixhauser Score was 6 (IQR 4, 7), and there were no significant differences between groups. In the overall cohort, there was a decrease in the monthly rate of indwelling urinary catheter use pre- versus post- intervention (Figure 1) of 182/1,000 vs 166/1,000 patient days, P = 0.03. There was also a decrease in rate of positive urine cultures from pre- to post- intervention (38/1,000 vs 28/1,000 patient days, P = 0.004). Antibiotic days of therapy (DOTs) for UTI indication was similar in the pre- versus post-intervention groups with 1.9/1000 vs. 1.8 DOT/1,000 patient days (P = 0.7). In the subgroup of 210 patients (73 pre- vs 137 post-intervention) who underwent urinalysis, there was also a decrease in the proportion of positive urine cultures from pre- to post-intervention (42.5% vs. 24.3%; P = 0.007). Of patient receiving antibiotics for UTI indication, appropriateness was numerically higher post-intervention (9.1% vs. 31.6%; P = 0.21). The use of external urinary catheters may be beneficial in reducing bacteriuria and related antibiotic use among female ICU patients. All Authors: No reported disclosures

The Clinical and Laboratory Standards Institute (CLSI) revised breakpoints for cefazolin (CFZ) may be difficult to implement with current automated susceptibility testing (AST) platforms and Enterobacterales may be falsely reported as susceptible to CFZ. The possibility remains that CFZ may then be inappropriately used as definitive therapy. This was a retrospective observational cohort of adult patients with Enterobacterales bloodstream infections (BSI) reported CFZ susceptible per Vitek®2 (bioMerieux, Durham NC). The primary outcome was the percentage of CFZ susceptible Enterobacterales isolates using three different susceptibility testing methods: Vitek®2 automated testing, ETEST® (bioMerieux, Durham NC), and disk diffusion. Secondary outcomes included treatment failure defined as a composite outcome of 30-day all-cause inpatient mortality, 30-day recurrent BSI, 60-day recurrent infection, or infectious complications. In 195 isolates reported CFZ susceptible per Vitek®2, 84 (43.1%) were CFZ susceptible using E-test vs.119 (61%) using disk diffusion (Figure 1). Rates of treatment failure were similar in both CFZ and non-CFZ groups (33.3% vs. 38.5% respectively; p=0.57). Both groups had high rates of ID consult involvement (>60%) and source control (>80%) with urinary tract being the most reported source. No difference was noted in 30-day all-cause mortality, secondary infectious complications, 30-day readmissions, or 60-day recurrent infections. A subgroup analysis of patients receiving CFZ vs. ceftriaxone suggests treatment failure was significantly less likely to occur in the setting of source control (adjusted OR 0.06; 95% CI, 0.13–0.32) and ID consult Figure 1: CFZ Susceptibilities by Testing Method There was a large discrepancy among testing methods; additional confirmatory CFZ susceptibility testing beyond AST platforms should be considered prior to definitive use of CFZ for systemic Enterobacterales infections. All Authors: No reported disclosures

Resistant gram-negative infections are becoming increasingly difficult to treat, prompting increased focus on drug development. This review will focus primarily on the new beta-lactam agents developed in the past 5 years that target multidrug-resistant (MDR) gram-negative organisms, including those producing carbapenemases. Four new agents including ceftazidime-avibactam (CAZ-AVI), meropenem-vaborbactam (MER-VAB), imipenem-relebactam (IMI-REL), and cefiderocol have recently been approved for the treatment of resistant gram-negative infections. CAZ-AVI remains an option for blaOXA-48–producing isolates and potentially MDR Pseudomonas aeruginosa, but the concern for resistance arises when using the agent for KPC-producing Enterobacteriales. MER-VAB appears to be more stable than CAZ-AVI in the treatment of KPC-producing Enterobacteriales but less is known about its propensity for the development of resistance and the drug does not reliably expand the coverage of meropenem-resistant P. aeruginosa isolates. IMI-REL expands the spectrum of imipenem-cilastatin to include KPC-producing Enterobacteriales as well as MDR P. aeruginosa but much less is known about its real-world clinical utility. Cefiderocol is the only of the four new agents with efficacy against metallo-beta-lactamases and resistant Acinetobacter species, but comparator studies using best available therapy for carbapenem-resistant gram-negative bacterial infections show higher mortality rates with the new drug, making its role in clinical therapy still to be determined. The new beta-lactams differ in their mechanisms of combatting resistance and thus have unique roles in therapy. Additional evidence is needed regarding the potential for development of resistance in the newer combination agents, as well as for the role of cefiderocol in carbapenem-resistant gram-negative infections.

Objective The aim of this study was to determine whether the current method of calculating a fosphenytoin reloading dose results in a therapeutic free phenytoin level on subsequent days. Methods Medical records of patients receiving fosphenytoin in the neurocritical care unit between July 2017 and June 2018 were screened. Included patients were those who had received at least three doses of fosphenytoin and required reloading doses according to concentrations obtained through therapeutic drug monitoring. Free phenytoin levels were categorized based on the prespecified patient-specific target range, generally between 1.5 and 2.5 mcg/mL. Results Of the fosphenytoin reloading doses administered, 48% (73/152) resulted in a therapeutic free phenytoin concentration on the subsequent day, with the remaining 52% resulting in nontherapeutic levels (39% subtherapeutic, 13% supratherapeutic). Our evaluation of reloading dose calculation strategies indicated that patients were two times as likely to obtain a therapeutic level when a modified pharmacokinetic equation omitting the use of volume of distribution or salt formulation was used (58%, n = 39) than they were with doses calculated using the current pharmacokinetic model (41%, n = 20) or doses based on provider preference (39%, n = 14). Conclusion The current method of calculating a fosphenytoin reloading dose in the critically ill population does not consistently result in therapeutic concentrations. With multiple factors affecting the pharmacokinetics of critically ill patients, the creation of a new pharmacokinetic model with less emphasis on volume of distribution may more consistently result in therapeutic concentrations.

Background: Chronic Hepatitis C virus (HCV) is an infection associated with an increased risk of cirrhosis, hepatocellular carcinoma (HCC), and morbidity and mortality. Treating HCV poses challenges in the elderly population due to the lack of evidence and complexity of patients. Objective: This study aims to evaluate factors that influence HCV treatment success in elderly patients, especially those over age of 70, such as pill burden and comorbidities, in addition to drug interactions and adverse effects. Methods: This was a retrospective chart review of patients treated at our urban academic institution from 2014-2016. Results: Sixty-two patients over the age of 70 were included in this study. The sustained virologic response rate 12 weeks after the completion of treatment (SVR12) was 79%. In a multi-variate analysis, cirrhosis, age closer to 70, and longer duration of treatment were statistically significantly more likely to lead to treatment failure. Though not statistically significant, other factors that may negatively influence achievement of SVR12 were cognitive impairment, cardiovascular disease, multi-tablet HCV regimen, time to initiation of HCV treatment > 90 days, and prior treatment experience. Pill burden of other prescribed medications did not impact SVR12. Adverse events and drug interactions were common in the population. Conclusions: Overall SVR12 rate in the elderly population was lower than that reported in the literature. Factors associated with lower treatment success, especially cirrhosis, should be considered when treating an elderly population. Further data is needed on the impact of other factors on SVR12 attainment in an elderly patient population. Article Type: Original Research